PROJECT SUMMARY/ABSTRACT The proposed research is to study radiant pressure effects of ultrasound on living tissues using animal models for cancer therapeutics. A major limitation of prior work regarding therapeutic effects of radiant pressure on cancer has been either too low acoustic intensity (in case of unfocused ultrasound produced with conventional transducers used for imaging) or too high acoustic intensity (in case of high-intensity focused ultrasound used to ablate tissue with thermal effects). Here, a novel Self-Focusing Acoustic Transducer (SFAT) capable of electrically varying the focal length and intensity will be used to deliver direct radiant pressure forces to living tissues, in the absence of thermal energy deposition or wide-spread cavitation formation, to preferentially kill cancer cells without damaging adjacent normal cells or tissue. Many studies have demonstrated that cancer cells are significantly more deformable (?less stiff?) than non-malignant counterparts. Our preliminary studies show that a focused acoustic beam within a specific energy range preferentially kills melanoma, prostate, and other cancer cells compared with non-tumorogenic matched cell lines. Further, our data supports that this is a direct result of fundamental differences in cytoskeletal architecture specific to malignant transformation. Thus, we propose studies to assess radiant pressure effects of highly focused US on normal and malignant tissue (as subcutaneous tumors and xenografts) in vivo. Since SFATs delivers the intended acoustic intensity only on its focal spot, it can produce unique effects at a local point without affecting other regions. Moreover, it is also capable of delivering acoustic energy through an intermediate solid or liquid, and is very well suited for non-invasive tumor treatment. Thus, the transducer and the scientific findings encountered on the way to its development will serve as a transformative technology broadly applicable for treatment of skin cancer and other malignancies.